The invention relates to a preparation of furan sulfonamide compounds useful in the synthesis of IL-1 inhibitors. It has now been surprisingly found that by using the electrophilic sulfonation of (C.sub.1 -C.sub.6)alkyl-3 furoate and subsequent functional group manipulation, the process to prepare furan sulfonamide compounds is simplified.
Aryl and hetero substituted urea derivatives are useful in the treatment of inflammation in joints, central nervous system, gastrointestinal tract, endocardium, pericardium, lung, eyes, ears, skin and urogential system. IL-1's status as an important mediator of inflammation is based on many studies demonstrating this cytokine's proinflammatory activity. These effects are manifest as stimulation of cartilage resorption, induction of leukocyte recruitment and the acute phase response, and the production of fever and a shock like state. The changes mediated by IL-1 binding to its receptor include regulation of adhesion molecules and chemokines, stimulation of metalloprotease synthesis, increased synthesis of cyclooxygenase-2 and phospholipase A2 thus increasing prostaglandin production, the induction of nitric oxide synthase thus increasing nitric oxide production and stimulation of IL-6 synthesis resulting in changes in the synthesis of acute phase proteins. Two distinct forms of IL-1 (IL-1 .alpha. and IL-1 .beta.) are produced by monocytes and macrophase in response to inflamatory stimuli. This is described in U.S. patent application Ser. No. 60/036,979.